The references cited herein are not admitted to be prior art to the claimed invention.
Cytochrome P-450 enzymes are an important enzyme system responsible for the metabolism of drugs, environmental chemicals, and endobiotics. Human cytochrome P-450 enzymes are present in multiple forms that are heterogeneously distributed in individuals and tissues. Multiple forms of P-450 enzymes have different substrate and product specificities that sometimes overlap. (Gonzalez Pharmacol. Rev. 40:243–288, 1988; Guengerish et al., Adv. Exp. Med. Biol. 283:1–11, 1991; Guengerish et al., Pharmacol. Ther. 54:17–61, 1992, Coon et al., FASEB J. 6:669–673, 1992; and Nelson et al., Pharmacogenetics 6:1–42, 1996.)
One type of P450 enzyme is P450 2D6 (also referred to as “CYP2D6”). CYP2D6 is a debrisoquine hydroxylase that functions in the metabolism of numerous drugs, and is polymorphically expressed. (Gelboin et al., Pharmacogenetics 7:469–477, 1977.)
Polymorphism of CYP2D6 was first identified in the human population due, in large part, to the role of CYP2D6 in the oxidation of debrisoquine/sparteine. Subsequent studies have shown that 5–10% of the Caucasian and 1% of the Asian populations carry the autosomal recessive trait for a poor metabolizer. (Conzalez, F. J. (1996) The CYP2D Subfamily. In Cytochromes P450: Metabolic and toxicological aspects. C. Ioannides and D. V. Parke (eds), CRC Press, Inc.)
Inhibitory monoclonal antibodies offer a simple and precise method for assessing the quantitative role of the different P450 enzymes in substrate metabolism. Monoclonal antibodies described as inhibiting CYP2D6 are referenced in Gelboin et al., Pharmacogenetics 7:469–477, 1997, Krausz et al., Biochemical Pharmacology 54:15–17, 1997, and U.S. Pat. No. 6,060,253.